3-endo-methyl-3-exo(4{40 -methylpentanalyl)-2-methylenebicyclo{8 2.2.1{9 heptane and process for preparing same

ABSTRACT

The compound, 3-endo-methyl-3-exo(4&#39;&#39;-methylpentanalyl)-2methylenebicyclo(2.2.1)heptane, and a process for preparing this compound are disclosed. 3-endo-Methyl-3-exo(4&#39;&#39;-methylpentanalyl)2-methylenebicyclo(2.2.1)heptane is valuable as a perfume component.

States 1 met Pieper et a1.

[5 3-ENDO-METHYL-3-EXO(4 METHYLPENTANALYL)-2-METHYLENEBICYCLO[2.2.1I-EPTANE AND PROCESS FOR PREPARING SAME [7 2]Inventors: Kenneth M. Pieper, West Chester; Thomas W. Gibson, ColerainTownship, Hamilton County, both of Ohio [73] Assignee: The Procter &Gamble Company, Cincinnati, Ohio [22] Filed: Sept. 3, 1969 21 Appl. No.:855,043

252/89 51 1111.01 .1c0747/3s [58] FieldoISearch ..260/598, 603R 1 51June 27, 1972 Sathe et 211., Indian Journal Chemistry, Vol. 4 (1966)pages 393- 395 Primary Examiner-Bemard Helfin AttorneyJulius P. FilcikABSIRACT The compound, 3-enclo-methyl-3-exo(4'-methylpentanalyl)-2-methylenebicyclo[2.2.1]heptane, and a process for preparing thiscompound are disclosed. 3-endo-Methyl-3-exo(4-methylpentanalyl)-2methylenebicyclo[2.2. 1 ]heptane is valuable as aperfume component.

6 Claims, No Drawings 3-ENDO-METHYL-3-EXO(4 '-METI'IYLPENTANALYL)-2-METHYLENEBICYCLO[ 2.2. lHEPTANE AND PROCESS FOR PREPARING SAL/[E FIELDOF THE INVENTION This invention relates to the compound 3-endomethyl-3-exo( 4'-methylpemanalyl )-2-methylenebicyclo[2.2.1 l-heptane, a compoundhaving a valuable sandalwood odor useful in perfume compositions and toa process for preparing 3- endo-methyl-3-exo(4'-methylpentanalyl)-2-methylenebicyclo[2.2.l]heptane from 3-endo-methyl-3- exo( 4methyl-5-hydroxypentyl)-2-methylenebicyclo[2.2. l ]heptane.

HISTORY OF THE INVENTION East Indian sandalwood oil has heretofore beenavailable only from East Indian sandalwood trees. This oil and variousindividual components of the oil are highly valued perfume bases and areused in large quantities by the perfume industry. The oil, however, isexpensive and is in limited, and sometimes sporadic, supply. For thisreason, a continuous effort has been made to synthesize the variouscomponents of sandalwood oil or similar synthetic materials whichpossess the desirable woody fragrance of sandalwood oil.

3-endo-Methyl-3-exo(4'-methylpentanalyl)-2-methylenebicyclo[2.2.l]heptane, dihydro-B-santalal, and the process forpreparing dihydro-fi-santalal represents a portion of an extensivescientific effort to prepare compounds having the valuablecharacteristics of sandalwood. Other processes and intermediatecompounds involved in this effort relating to the synthesis of syntheticsandalwood oil components and specifically to the synthesis ofdihydro-fl-santalol, a starting material used in the process forpreparing dihydro-B-santalal, are described in the following copendingUS. applications: Fanta and Erman,3-endo-Methyl-3-exo(4'-methyl-5'-hydroxypentyl)norcamphor and2-Methyl-5-bromopentanol, and Process for the Preparation of TheseCompounds, Ser. No. 717,360, filed Mar. 29, 1968 and now US. Pat No.3,579,479; Fanta and Tetrahydropyranyl Tetrahydropryranyl EtherCompounds and Process for Preparation of These Compounds and3-endo-Methyl-3-exo(4-methyl-5'-hydroxypentyl)norcamphor, Ser. No.717,384, filed Mar. 29, 1968 and now abandoned; Fanta and Erman,Preparation of 3-endo-Methyl- 3-exo(4-methyl-5'-hydroxypentyl)norcamphorfrom 2- Methyl-4-pentenol, Ser. No. 717,362, filed Mar. 29, 1968 and nowUS. Pat. No. 3,580,953; Fanta and Erman, Preparation of3-endo-Methyl-3-exo-(4-methyl-5-hydroxypentyl)norcamphor from2-Methyl-4-pentenol, Ser. No. 717,458, filed Mar. 29, 1968; Kretschmar,Fanta and Erman, Process for Preparing 3-endo-Methylnorcamphor from2-Methylnorbom- 2-ene, Ser. No. 731,653, filed May 23, 1968; Gibson,Kretschmar and Erman, Process for Preparing 3-Methylnorcamphor from2-Methylmorborm-2-ene, Ser. No. 731,652, filed May 23, 1968; 1968; Fantaand Erman, Process for Preparing Dihydro-B-Santalol from3-endo-Methyl-3-exo(4- methyl-5' hydroxypentyl)norcamphor Ser. No.753,897, filed Aug. 20, 1968; Fanta and Erman, Process for PreparingDihydro-Bsantalol from 3-endo-Methyl-3-exo(4-methyl-5'-hydroxypentyl)norcamphor, Ser. No. 779,233, filed Nov. 26, 1968;Kretschmar and Erman, Process for Preparing B-Santalol from3-methylnorcamphor, Ser. No. 826,628, filed May 21, 1969; and Kretschmarand Erman, Process for Preparing B-Santalol from 3-Methylnorcamphor,Ser. No. 826,684, filed May 21, 1969.

SUMMARY OF THE INVENTION This invention relates to dihydro-fl-santalol,3-endomethyl- 3-exo( 4'-methylpentanalyl)-2-methylenebicyclo-[2.2. 1]heptane, which is a valuable synthetic perfume component having adesirable sandalwood odor. Dihydro-B-santalal has the structural formulashown below.

CHO

PROCESS FOR PREPARING DIHYDRO-B-SANTALAL Dihydro-Bsantalal, the productof the above process and the novel compound described in this inventionpossesses a desirable, woody sandalwood fragrance, and has utility as aperfume component.

The initial starting compound used in the process of this invention isdihydro-B-santalol. Processes for preparing this compound fromcommercially available starting materials are described in the followingcopending US. Pat. applications: Fanta and Erman,3-endo-Methyl-3-exo(4'-5-hydroxyphentyl)norcamphor and2-Methyl-5-bromopentanol, and Process for the Preparation of Thesecompounds, Ser. No. 717,360, filed Mar. 29, 1968; Fanta and Erman,Tetrahydropyranyl Ether Compounds and Process for the Preparation ofThese Compounds and3-endo-Methyl-3-exco(4-methyl-5'-hydroxypentyl)norcamphor, Ser. No.717,384, filed Mar. 29, 1968; Fanta and Erman, Preparation of3-endo-Methyl-3-exo(4'- methyl-5'-hydroxypentyl)-norcarnphor from2-methyl-4-pentyl, Ser. No. 717,362, filed Mar. 29, 1968; Fanta andErman, Preparation of3-endo-Methyl-3-exo(4'-methyl-5'-hydroxypentyl)norcamphor, Ser. No.717,374, filed Mar. 29, 1968; and Fanta and Erman, Process for PreparingDihydro-B-Santalol from3-endo-Methyl-3-ex0(4'-methyl-5'-hydroxypentyl)norcamphor, Ser. No.779,233, filed Nov. 26, 1968.

The process for preparing dihydro-B-santalal described herein comprisesreacting dihydro-B-santalol whose structural formula is shown above withan oxidizing agent selected from the group consisting of chromic acidand chromium trioxidepyridinium complex. The hydroxyl functional groupof the side chain is oxidized to a carbonyl group.

A reaction mixture comprising dihydro-B-santalol in a solvent isgenerally prepared. Examples of solvents which can be used are ketones,such as acetone, methyl ethyl ketone and pentanone, aromatic hydrocarbonsolvents, such as benzene, xylene or toluene and chlorinated hydrocarbonsolvents, such as methylene chloride, methyl chloride, carbontetrachloride and chloroform. Mixtures of these solvents, e.g., in a 1:1weight ratio are also suitable. Methylene chloride and a mixture ofacetone and benzene in a 1:1 weight ratio are the preferred solvents.Generally the solvent is used in a weight ratio to thedihydro-B-santalol of from 1:1 to 1,000:1 preferably 20:1 to 100:1.

The oxidizing agents suitable for use in the process of this inventionare chromic acid and chromium trioxide-pyridinium complex. Theseoxidizing agents are described separately hereinafter.

Where chromic acid is used as the oxidizing agent it is prepared bymixing chromium trioxide with a mineral acid such as sulfuric acid. Whensulfuric acid is used as the mineral acid a molar ratio of from 1:1.5 to1:3 of chromium trioxide to sulfuric acid is usually used. An aqueoussolution of the chromium trioxide/sulfuric acid mixture is then preparedby mixing the chromium trioxide/sulfuric acid mixture with water in aconcentration range of 0.5 to 5 molar. This aqueous mixture is thengenerally added dropwise to the dihydro-fi-santalol/solvent mixture withstirring, e.g., titrated into the dihydro-B-santolol/solvent mixture.The chromium trioxide oxidizing agent is generally used in the correctstoichiometric molar ratio to the dihydro-B-santalol, i.e., 1:1.5. Anexcess is not preferred so as to minimize oxidation of the aldehydefunctional group of the dihydro-B-santalal to a carboxylic acidfunctional group.

Where chromium trioxide-pyridinium complex is used the oxidizing agentgenerally is prepared by dissolving chromium trioxide in pyridine in aweight ratio of from 1:5 to 1:20 of chromium trioxide to pyridine. Thechromium trioxidepyridinium complex formed is recrystallized from thesolution and is then dissolved in a solvent in a weight ratio of from1:1 to 1:1,000 preferably from 1 :20 to 1:100 for use in the process forpreparing dihydro-B-santalal. Suitable such solvents for use arearomatic hydrocarbon solvents such as benzene, xylene and toluene orchlorinated hydrocarbon solvents such as methylene chloride andchloroform. Mixtures of these solvents can be used where desired, e.g.,in a 1:1 weight ratio. Methylene chloride is the preferred solvent wherethe chromium trioxide-pyridinium complex is used as the oxidizing agent.Where the chromium trioxide-pyridinium complex is used, it generally isused in a 6:1 to 20:1 molar ratio to the dihydroB- santalol, preferablyin a 6:1 to 10:1 molar ratio.

The oxidizing agents are generally added to the solvent mixturecontaining the dihydro-B-santalol in a dropwise manner. The solutionnormally is cooled in order to prevent excess heating on reacting and tocontrol the reaction temperature more easily. Dropwise addition withstirring is preferred because localized concentration of oxidizingagents which could lead to degradation and production of by-products isminimized.

The reaction is normally an instantaneous one and temperatures aroundroom temperature or below, e.g., to 30 C., can be used and are generallypreferred. However, temperatures ranging from 70 to 50 C. can be usedwhere desired. The process can be performed in air and it is notnecessary to conduct the reaction in an inert atmosphere. An inertatmosphere of argon or helium can be used where desired.

Generally the reaction proceeds during the addition of the oxidizingagent. Additional stirring can be used where desired, however, since thereaction is essentially instantaneous additional stirring is of no realadvantage in increasing the yields of dihydro-B-santalal obtained.Generally the time of the reaction will range from less than 5 minutesto approximately an hour depending upon the amount of dihydro-B-santalalto be oxidized and the concentrations used.

Once the reaction has been completed clihydro-B-santalal is obtained.Separation of the dihydro-B-santalal can be obtained by conventionaltechniques, e.g., distillation of the reaction mixture or separation ofthe product from the reaction mixture by fractional crystallization orcolumn chromatography.

Dihydro-fi-santalal prepared as described above, the highly desirableand useful odor properties characterized as strong sandalwood.Dihydro-B-santalal can be used as a component of perfume compositionsfor ultimate use in products such as soaps, detergents, deodorants, andthe like. Perfume compositions containing odoriferously effectiveamounts, e.g., 0.001 to about 50 percent of dihydro-,B-santalal, aredesirable and useful. More specific illustrations of the perfume utilityof this compound are found in Examples 11 to IV given hereinafter.

EXAMPLES The following examples illustrate the specific embodiments ofthis invention and are not intended to be limiting. All percentages andratios in the following examples as well as in the specification and theappended claims are by weight unless otherwise indicated. Thetemperatures are expressed in degrees centigrade. Boiling points are notcorrected.

Data listed in all the examples were obtained by means of the followingtechniques unless otherwise indicated. Infrared spectra were determinedon a Perkin-Elmer Model 137 Infracord spectraphotometer. Nuclearmagnetic resonance (nmr) spectra were determined in carbon tetrachloridewith a Varian Model PIA- spectrometer with tetramethylsilane (101') asan internal reference. The nmr data are in the odor chemical shift,integration, multiplicity, coupling constant (in Hz), and assignment.

EXAMPLE 1 Preparation of 3-endo-methyl3-exo(4'-methy1pentanalyl)-2-methylenebicyclo[2.2. l ]heptane A. Preparation of starting material,dihydro-B-santalol The starting compound for this preparation,dihydro-B-santalol, was prepared according to the process set forth inExample 1 of U.S. Pat. No. 3,579,479. In this process, commerciallyavailable 2-methyl-4-pententol is borated with boric acid to form tri(2-methyl-4-pentenyl)borate. The borate is hydrobrominated by freeradical addition and then hydrolyzed to obtain 2-methyl-5-bromopentanol.The 2-methyl-5- bromopentanol is borated with boric acid and,subsequently, this product is reacted with the enolate of3-methylnorcamphor and then hydrolyzed to form 3-endo-methyl-3-exo(4-methyl-5-hydroxypentyl)norcamphor. 3-Methylnorcamphor was preparedaccording to the process described in the patent application of Gibson,Kretschmar and Erman, for Process for Preparing 3-Methylnorcamphor fromZ-methylnorbom-2-ene, Ser. No. 731,653, filed May 23, 1968, by reactingmethylcyclopentadiene dimer and ethylene according to the method ofAlder and Ache, Chem. Ber. 95, p. 503 (1962) to obtain2-methylnorbom2-ene. The Z-methylnorborn-2-ene was then reacted with aperacid such as perbenzoic acid and subsequently with a catalytic amountof a Lewis or mineral acid to obtain 3-methylnorcamphor. The3-endomethyl-3-exo(4'-methyl-5'-hydroxypentyl)norcamphor is then used asan intermediate in the process described in the copending U.S. patentapplication of Fanta and Erman, having Ser. No. 779,233 filed Nov. 26,1968, entitled Process for Preparing Dihydro-B-santalol from3-endo-Methyl-3-exo(4- methyl-5'-hydroxypentyl)norcamphor, Example 1,pages 12 to 15. In the disclosure therein the 3-endo-methyl-3-exo(4'-methyl-5-hydroxypentyl)norcamphor is borated to obtain the borate ester,tri[3-endo-methyl-3-exo(4'-methyl-5'-hydroxpentyl)norcamphor]borate.This borate ester is then reacted in strong base with a phosphoruscompound, such as methyltriphenylphosphonium bromide, and hydrolyzed toobtain dihydro-B-santalol.

B. Preparation of dihydro-B-santalol A 11.1 g. sample ofdihydro-B-santalol prepared as described above was dissolved in 400 ml.of acetone and titrated at 0 C. with a 2.67 molar solution of chromiumtrioxide in aqueous sulfuric acid (4.1 M) according to the method of A.Bowers et al., J. Chem. Soc., 2548 (1953). A small amount of isopropylalcohol was added to destroy any excess oxidant, and most of the solventwas removed under vacuum.

The residue was washed with ether (three times). The ether extracts wereseparated and combined. After washing the ether extracts with base,distillation of the reaction mixture gave 3 g. of dihydro-B-santalal(b.p. l051 15 C. at 0.15 mm. Hg). Six grams of a 1:1 mixture of thestarting alcohol and dihydro-B-santalal (b.p. 115 C. at 0.15 mm. Hg)were also obtained resulting in a 54 percent yield of dihydro-62-santalal.

An analytical sample of dihydro-B-santalal was obtained by collecting asample from an Aerograph Model 202-18 gas chromatograph containing a5ft. X A inch, 20 percent SE-30 stainless steel column. This purifiedmaterial gave )t 5.85 6.04, and 11.4 2 and nmr signals at 19.0 (3H, s),8.96 (3H, d, J =6.6 Hz), 5.59 (ll-l, r), 5.31 (1H, s), 0.39 (1l-l,d, .I=2 Hz). A mass spectrum of the compound on an Atlas SM-l spectrometergave a molecular weight of 220 when a cold temperature inlet wasutilized.

When in the above examples other oxidizing agents, e.g., chromiumtrioxide-pyridinium complex, are substituted on an equivalent basis ofthe chromium trioxide in aqueous sulfuric acid used above, substantiallysimilar results are obtained in that dihydro-B-santalol is oxidized todihydro-B-santalal. When in the above example other solvents are used,e.g., aromatic hydrocarbon solvents such as methylene chloride,chloroform or carbon tetrachloride and mixtures of these solvents in a1:1 weight ratio, are substituted on an equivalent basis for the acetoneused substantially similar results are ob tained in thatdihydro-fi-santalol is oxidized to dihydro-B-santalal.

EXAMPLE 11 Perfume Compositions Perfume compositions containingdihydro-B-santalal are prepared'by mixing the components shown below inthe amounts indicated. The compositions exhibit highly desirable anduseful odors.

Composition ANarcissus Component Percent by Weight Dihydro-fl-santalol8.00 Dihydro-flmantalal 2.00 Neroli 011 4.00 Vetivert oil 12.50 lsobutylsalicylate 14.50 Phenylacetic aldehyde 5.00 Paracresyl acetate 20.00Ylang ylang 8.50 Heliotropin 5.50 Cinnamic alcohol 20.00

Composition B-Chypre Component Percent by Weight Essence oakmoss 5.00Bergamot oil 22.50 Vetivert oil 7.50 Oil of lavender 5.00Dihydro-fi-santalol 6.00 Dihydro-fl-santalal 1.00 Patchouli 1.00 Clovebud oil 3.50 Jasmine complex 10.00 Rose complex 8.00 lsobutyl salicylate7.00 Cinnamic alcohol 5.00 Heliotropin 10.00 Coumarin 5.00 Resin aromaof tonka bean 2.00 1.50

Methyl nonyl acetic aldehyde The components and proportions in theperfume compositions of this example can be adjusted according tomethods well known in the perfume art to form a wide variety ofdesirable perfume compositions containing odoriferously effectiveamounts of these compounds EXAMPLE lll Soap Bar Composition Aconventional household soap bar having the following composition isprepared:

Component Percent by Weight Sodium soap 75.0 Potassium soap 7.5

(The total soap comprises a mixture of tallow soap and 20% coconut soap)Water 15.0 Perfume composition A of Example 11 2.5 TOTAL 100.0

This soap bar exhibits a desirable narcissus fragrance. Com position Bof Example I can be substituted for Composition A in the above soap barcomposition to attain a chypre fragrance.

EXAMPLE IV Detergent Composition A conventional, granular, heavy-dutybuilt detergent having the following composition is prepared:

The detergent composition exhibits a desirable narcissus fragrance.Composition B of Example 11 can be substituted for Composition A toattain a highly desirable chypre fragrance.

What is claimed is:

1. 3-endo-Methyl-3-exo(4-methylpentanaly1)-2- methylenebicyclo[2.2. 1]heptane.

2. A process for preparing3-endo-methyl-3-exo(4'-methylpentanalyl)-2-methy1enebicyc1o[2.2. 1]heptane comprising oxidizing3-endo-methyl-3-exo(4'-methyl-5'-hydroxypentyl)- 2-methylenebicyclo[2.2.l ]heptane with an oxidizing agent wherein said oxidizing agent ischromium trioxide-pyridinium complex.

3. The process of claim 2 wherein 3-endo-methyl-3-exo(4- methyl-5-hydroxypentyl)-2-methylenebicyclo[ 2.2. 1 ]heptane is dissolved in asolvent in a molar ratio to the solvent of from 1:1 to 111,000.

4. The process of claim 3 wherein the chromium trioxidepyridiniumcomplex is prepared by dissolving chromium trioxide in pyridine in aweight ratio to pyridine of 1:5 to 1:20, recrystallizing the chromiumtrioxide-pyridinium complex, and subsequently dissolving the chromiumtrioxide-pyridinium complex in a solvent in a weight ratio to solvent offrom 5. The process of claim 4 wherein the chromium trioxidepyridiniumcomplex is used in a molar ratio to the3-endomethyl-3-exo(4'-methyl-5'-hydroxypentyl)-2- methylenebicyclo[2.2.l ]heptane of 6:1 to 20:1.

6. The process of claim 5 wherein the reaction temperature ranges from70 to 50 C.

2. A process for preparing3-endo-methyl-3-exo(4''-methylpentanalyl)-2-methylenebicyclo(2.2.1)heptanecomprising oxidizing 3-endo-methyl-3-exo(4''-methyl-5''-hydroxypentyl)-2-methylenebicyclo(2.2.1)heptane with an oxidizing agent wherein saidoxidizing agent is chromium trioxide-pyridinium complex.
 3. The processof claim 2 wherein 3-endo-methyl-3-exo(4''-methyl-5''-hydroxypentyl)-2-methylenebicyclo(2.2.1)heptane is dissolved in a solvent in a molarratio to the solvent of from 1:1 to 1:1,
 000. 4. The process of claim 3wherein the chromium trioxide-pyridinium complex is prepared bydissolving chromium trioxide in pyridine in a weight ratio to pyridineof 1:5 to 1:20, recrystallizing the chromium trioxide-pyridiniumcomplex, and subsequently dissolving the chromium trioxide-pyridiniumcomplex in a solvent in a weight ratio to solvent of from 1:1 to1:1,000.
 5. The process of claim 4 wherein the chromiumtrioxide-pyridinium complex is used in a molar ratio to the3-endo-methyl-3-exo(4''-methyl-5''-hydroxypentyl)-2-methylenebicyclo(2.2.1)heptane of 6:1 to 20:1.
 6. The process of claim5 wherein the reaction temperature ranges from -70* to 50* C.